First‐in‐human phase I study of E7090, a novel selective fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors

Fibroblast growth factor receptors (FGFR) are a family of transmembrane receptor tyrosine kinases involved in regulating cellular processes. FGFR mutations are implicated in oncogenesis, representing therapeutic potential in the form of FGFR inhibitors. This phase I, first‐in‐human study in Japan evaluated safety and tolerability of E7090, a potent selective FGFR1‐3 inhibitor, in patients with advanced solid tumors. Dose escalation (daily oral dose of 1‐180 mg) was carried out to assess dose‐limiting toxicity (DLT), maximum tolerated dose, and pharmacokinetics. Pharmacodynamic markers (serum phosphate, fibroblast growth factor 23, and 1,25‐(OH)2‐vitamin D) were also evaluated. A total of 24 patients refractory to standard therapy or for whom no appropriate treatment was available were enrolled. No DLT were observed up to the 140‐mg dose; one patient in the 180‐mg cohort experienced a DLT (increased aspartate aminotransferase/alanine aminotransferase, grade 3). The maximum tolerated dose was not reached. Dose‐dependent increases in the maximum concentration and area under the curve from time 0 to the last measurable concentration were observed up to 180 mg. Dose‐dependent increases were observed in all pharmacodynamic markers and plateaued at 100‐140 mg, indicating sufficient FGFR pathway inhibition at doses ≥100 mg. In conclusion, E7090 showed a manageable safety profile with no DLT at doses ≤140 mg. Maximum tolerated dose was not determined. The recommended dose for the follow‐up expansion part, restricted to patients with tumors harboring FGFR alterations, was determined as 140 mg, once daily. This phase I, first‐in‐human study in Japan evaluated the safety and tolerability of E7090, a selective fibroblast growth factor receptor (FGFR) 1‐3 inhibitor, for treatment of advanced solid tumors. A total of 24 patients refractory to standard therapy or for whom no appropriate treatment was available were enrolled; no dose‐limiting toxicities were observed up to 140 mg QD and the maximum tolerated dose was not reached. E7090 showed an acceptable safety profile with dose‐dependent pharmacokinetic/pharmacodynamic parameters; preliminary efficacy will be investigated in a follow‐up expansion part restricted to gastric cancer patients with FGFR2 amplification or cholangiocarcinoma with FGFR2 fusion.